It has been reported that improvements in drug performance can be achieved by incorporating deuterium into specific sites of the active agent of certain approved pharmaceuticals. Examples include paroxetine (see WO 2007/016431 and US2007/0112031) and tadalafil (see US2007/0191381). The above-mentioned drugs all comprise benzo[d][1,3]dioxole groups. The methylenedioxy carbon of the benzo[d][1,3]dioxole group in paroxetine and tadalafil is one of the positions where deuterium incorporation is reported to provide for improved drug performance. The structures of benzo[d][1,3]dioxole and d2-benzo[d][1,3]dioxole (i.e., benzo[d][1,3]dioxole with two deuteriums at the methylenedioxy carbon) are shown below:

However, site-specific deuterium incorporation adds another level of complexity in developing suitable commercial syntheses. Specifically, reactions used to incorporate the deuterium should use reagents that are economical and that result in both a high chemical and isotopic yield. Total syntheses of paroxetine, tadalafil and the natural product berberine typically utilize benzo[d][1,3]dioxole derivatives as synthetic intermediates. Benzo[d][1,3]dioxole derivatives are typically made by reacting 1,2-catechols with dihalomethanes (CH2XY, wherein X and Y are halides that are the same or different):
Using deuterated dihalomethanes (CD2XY) to prepare d2-benzo[d][1,3]dioxole results in low incorporation of deuterium into the benzo[d][1,3]dioxole product, i.e., typically no greater than about 94% deuterium incorporation at each labeled site:
The low isotopic yield is less than desired for commercial syntheses of deuterated analogues of paroxetine, tadalafil and berberine comprising d2-benzo[d][1,3]dioxole groups.